The invention relates to a method and an apparatus for the selective in situ separation and enrichment of substances.
Separation, isolation and disintegration constitute a unit in most separation methods in biology and medicine. Biological material is disintegrated for the purpose of subsequent enrichment, separation or isolation of individual substances or groups of substances or compartments.
The isolation of substances from the most diverse biological materials has been a long-standing practice. Both unambiguous characterization and use in various fields such as pharmacy or medicine, for example, in most cases require the chemically uniform compound, i.e. the pure substance. Within the entire life science sector, therefore, separation methods represent one of the most important foundations for the identification of substances and their use. Said isolation or separation often constitutes a problem, depending on the specific isolation task, for example regarding the purity of the substance to be isolated.
The isolation, separation or disintegration of biological material, for example organisms, tissues, biological cells, organelles, micelles, viruses etc., as a rule constitutes the first step in the analysis or extraction of cell constituents. Such constituents can, for example, be nucleic acids, proteins, metabolites, pigments etc. As the quality of all subsequent steps is determined by the disintegration of the biological material, said disintegration occupies a key position. Novel disintegration methods are therefore of interest for a multiplicity of procedures and have a proportionately large potential for being marketed profitably as a product. Disintegration methods are a prerequisite, in the same way as explained above for the separation methods, for life science fields, for example genomics, proteomics and many others. Methods of disintegrating biological material are not universal, but are geared very specifically to the particular requirements. The known methodsxe2x80x94mechanical and nonmechanical disintegration methodsxe2x80x94are toxic, expensive, time-consuming and laborious, as well as being limited to specific applications. Moreover, there is a high risk of cross-contamination which has a major impact on the quality of all subsequent process steps, especially in sensitive detection methods such as, for example, the PCR-based nucleic acid detection methods. With the known mechanical methods, moreover, standardization and automation is more difficult, or it is virtually impossible to combine them with separation and isolation methods.
The standard separation and isolation methods include filtration, centrifuging, crystallization, distillation, extraction, electrophoresis, chromatography and magnetism-based methods.
Finally, a distinction is drawn between analytical and preparative methods. Analytical methods are used to detect specific substances in mixtures, while preparative methods are employed for concentrating or extracting larger quantities of as pure a substance as possible.
The use of pulsed electric fields for separation purposes has not been known hitherto.
Instead it is known to use such fields within the context of electroporation (Prausnitz, M. R. et al., in Biophysical Journal 66 (1994), 1522-1530, U.S. Pat. No. 5,019,034, U.S. Pat. No. 5,273,525, U.S. Pat. No. 5,304,120, U.S. Pat. No. 5,389,069, U.S. Pat. No. 5,422,272). With electroporation, from one to at most ten electric pulses (impulse number) are used, as a rule, over the particular treatment time. Depending on the pulse frequency, the treatment duration is at most a matter of seconds, the field strength of the pulses being chosen such that the critical voltage (Vc, equal to about 1 volt) across the membrane of the cell to be electroporated is exceeded (with spherical objects, the relationship v=3/2 E0r applies, where r is the cell radius). Electroporation is generally carried out under mild conditions, i.e. for example at room temperature, it being essential not to exceed or drop below the maximum physiologically acceptable temperature of the respective target organism or target cell (U.S. Pat. No. 5,466,587, U.S. Pat. No. 5,545,130, U.S. Pat. No. 5,547,467, U.S. Pat. No. 5,749,847).
Similar conditions are employed with cell fusion, the emphasis here too being on the choice of the mildest conditions possible, to achieve a high success rate in the fusion aimed for (xe2x80x9cElectroporation and Electrofusionxe2x80x9d in: Cell Biology, Plenum Press, New York and London (1989), editors: Neumann, E., Sowers, A. E. and Jordan, C. A.).
Finally, to achieve complete disruption of biological cells, pulsed electric fields are likewise used in some cases, the cell constituents being released uncontrolledly. In the process, pulse numbers greater than 20,000 are generally used, the field strength as with electroporation generally being above the critical voltage (Vc) of 1 volt across the membrane of the cell to be disrupted. The temperatures used for disruption of the biological cells are generally quite high, i.e. they are far above the physiologically suitable temperatures, since the aspect of cell preservation no longer plays a part and, in contrast, the disruption is to be accelerated and completed by employing extreme conditions (U.S. Pat. No. 5,235,905, U.S. Pat. No. 5,447,733, U.S. Pat. No. 5,393,541).
It is hitherto unknown, by means of the conventional methods, for biological material to be sorted, separated and disintegrated and for substances to be released and to be concentrated or isolated directly, or to be purified. Conventional methods, especially separation methods are generally preceded by a time-consuming and expensive sample preparation after cell disruption or work-up, especially sorting and/or disintegration, of the biological material. Thus, the biological material is often first homogenized and lysed, and then is subjected to further processing steps and finally to the separation method. Only in exceptional cases can the homogenate be subjected directly to a separation method. Usually, however, the homogenate is then centrifuged and the supernatant as a crude extract is subjected to a separation method, first requiring adjustment of pH, ionic strength and other parameters.
The object of the invention is therefore to provide a method of separating and disintegrating substances from and/or on biological materials, which renders time-consuming and expensive sample preparation unnecessary and in a single process step leads to the selective in situ release and/or separation of the desired substance(s), a further object of the method being to enable a universal, standardized and consequently automated separation or disintegration of biological material, e.g. organisms, tissues, cells, organelles, micelles, viruses etc., in conjunction with the release of the constituents.
The present invention achieves this object by providing a method for the selective in situ separation of one or more substances from a substance mixture present in a liquid medium by means of a stationary and a mobile phase, wherein the stationary phase is a constituent of a biological material present in the liquid medium and the mobile phase is the liquid medium and wherein the biological material present in the liquid medium is subjected to pulsed electric fields having a field strength of up to 200 V/cm. The substance mixture to be separated can, prior to the separation, disintegration, isolation or enrichment according to the invention, be present in the biological material, or outside it, or both. This means that the substance mixture can be present directly in the liquid medium or enclosed in the biological material in the liquid medium. Preferably, in the process, i.e. during and/or after the treatment with the pulsed, electric fields, one or more desired substances are released from the biological material, are concentrated in the liquid medium and can then be separated from the biological material by means of conventional methods such as e.g. centrifuging or filtration of other, undesirable substances and/or the biological material. In a further preferred, alternative embodiment of the invention, one or more substances are concentrated in the biological material, thus abstracted from the liquid medium outside the biological material, and the liquid medium is then separated from the biological material outside the biological material, for example by centrifuging or filtration.
In a preferred embodiment the invention therefore envisages a purification of one or more substances being carried out directly in situ with the biological material, the substance(s) being released in situ in a single step and being separated from other undesirable substances. The present procedure in a preferred embodiment therefore combines the steps of cell disruption and substance isolation. In so doing, the biological material, especially its solid components such as cell skeleton and membranes, serves as a kind of stationary phase, while the liquid medium, both inside and outside the biological material, can be regarded as the mobile phase. The method is distinguished by extraordinary simplicity and speed, no longer demanding either a time-consuming sample preparation requiring a large amount of material, or cell disruption. Depending on the biological material, various types of interaction can be utilized simultaneously for the separation or the enrichment of substances.
The method is a method for the separation, isolation and/or disintegration of biological material in an electric field having a field strength of up to 200 V/cm. The method can be utilized, in particular, for cell disruption requiring little time and material.
The method is universally applicable and can be used, for example, for the separation of pharmacologically interesting proteins or for determining multiple equilibria between various substances in biological systems.
In connection with the present invention, the term xe2x80x9cbiological materialxe2x80x9d relates to spatial units enclosed by lipid or lipoprotein layers having a single- or two-layer structure, i.e. compartments such as cells, especially human, animal, vegetable, yeast or bacterial cells, cell aggregates, remnants or parts thereof, cell compartments such as endoplasmatic reticulum, plastids, mitochondria or cell nuclei, fused cells or cells undergoing division, artificial cell systems, liposomes or other multicomponent systems of natural or synthetic origin. The biological material includes a solid component, for example cell skeleton and membranes, also referred to as the stationary phase, and a liquid component, e.g. cytoplasmatic fluid.
In connection with the present invention, the xe2x80x9cseparation of one or more substancesxe2x80x9d refers to the preferably essentially osmosis- or diffusion-driven operation of specifically changing concentrations of one or more substances inside and outside the biological material, especially that of separating one or more substances from other substances, the one or more substances being selected from a selection of substances likewise present in the liquid medium i.e. from a substance mixture. The electric field applied also allows electrophoretic effects to serve or to be utilized as a driving force for increasing or decreasing the concentration of a substance.
In connection with the present invention, the term xe2x80x9csubstance(s) to be separatedxe2x80x9d relates to all substances that can be separated by means of the method according to the invention, especially nucleic acids such as DNA and RNA, in cyclic or linear form, proteins or peptides including those in derivatized form such as glycoproteins, or carbohydrates, including those in derivatized form such as proteoglycans. Of course it is also possible to separate other substances, be they of natural or synthetic origin, such as pigments, metabolites, natural substances, synthetic macromolecules and the like. The term xe2x80x9csubstancexe2x80x9d does not, for example, cover the solvent, e.g. water.
In connection with the present invention, the term xe2x80x9cenrichmentxe2x80x9d refers to an increase in the concentration and xe2x80x9cdepletionxe2x80x9d to a decrease in the concentration.
In connection with the present invention, the term xe2x80x9cdisintegrationxe2x80x9d refers to a process which modifies the state of order of biological material or which initiates or accompanies the modification. A cell, especially one without defects, has a high state of order which, for example, can be altered by lytic processes at the cell membrane, as a result of compartments of the cell diffusing into the solution surrounding it. For the purpose of the invention, a method of separation, especially of selective separation, and/or enrichment can also be a disintegrating method.
In connection with the present invention, the term xe2x80x9cliquid mediumxe2x80x9d refers to a preferably aqueous solution, suspension or emulsion. The liquid medium within the biological material can differ, in terms of its composition, from the composition outside the biological material, for example be in the form of plasma within a cell and in the form of saline outside the cell.
The present invention is based, inter alia, on the use of pulsed electric fields to treat biological material, the generated potential difference across the membrane of the biological material preferably, depending on the biological material itself, on pulse number, pulse shape, treatment duration and temperature, being below the critical voltage. Vc, resulting in the formation of permanent or transient pores of different diameters in the membrane. According to the invention it is of course also possible to provide potential differences across the membrane of the biological material which are above the critical voltage Vc. Through the pores formed, extracellular substances can pass into the biological material, especially the cell, intracellular substances conversely being released. The release or uptake of the substances depends on the strength and type of the interactions between these substances and between the substances and the biological material, on the lifetime and on the diameter of the pores. The biological material, including any intracellular matrix present of the membranes and cell walls present, e.g. tubulines etc., as the xe2x80x9ccell skeletonxe2x80x9d, takes part in the separation.
In a preferred embodiment, the invention provides a method for a chromatography-like, selective separation of substances in situ by means of a stationary and a mobile phase, wherein the stationary phase is a constituent of the biological material and the mobile phase is a liquid medium and wherein the biological material present in the liquid medium is subjected to pulsed electric fields having field strengths of up to 200 V/cm and the substance(s) of interest are released from the biological material, are concentrated in the liquid medium outside the biological material and are separated from the biological material. The invention therefore advantageously provides for the enrichment or separation to take place in situ, i.e. in and on the biological material containing the substances of interest, without the biological material having to be disrupted prior to the separation or enrichment. For separation purposes, centrifuging methods can be used according to the invention which are able to separate the substance(s) from the biological material. Alternatively, according to the invention, provision can be made for the separation of the biological material from the liquid medium present outside the biological material to be performed by filtration, crystallization, extraction, electrophoresis, chromatography or by means of similar methods.
A prerequisite for implementing the in situ separation method according to the invention is that the various parameters which affect the separation efficiency, such as field strength, pulse number, pulse shape, treatment duration, temperature, solution, type of biological material etc., be optimized for each isolation task to be carried out.
In a preferred embodiment, the invention makes provision for biological material to be disintegrated in a sample mount system, the sample mount system comprising at least one nonconductive element and two conductive elements, wherein a voltage is applied to the conductive elements and the biological material is exposed in an electric field having a field strength of up to 200 V/cm, particularly in a range of from 5 to 50 V/cm.
In a further preferred embodiment of the invention, the electric field acting on the biological material is homogeneous or inhomogeneous. Preferably, the disintegration or separation of the organisms, cells or compartments takes place in an inhomogeneous electric field.
In a preferred embodiment of the invention, the electric field line density is increased locally. The disintegration or separation, especially selective separation from biological material advantageously takes place in an inhomogeneous electric field in which, for example, the electric field line density can be locally increased.
In a further preferred embodiment it is advantageous for the number of the electric pulses to be above 10. The pulse number can be determined from the product of treatment duration and frequency. Depending on the sample to be treated, the treatment duration can be between a few seconds and a number of hours. The frequencies used in this context should be between a few mHz and more than 1 GHz. Via the selected frequency, it is possible to suitably limit the maximum pulse duration. The pulse duration can be a few nanoseconds but advantageously equally be in the range of a few minutes.
In a further preferred embodiment of the invention, the pulsed electric fields used can have various pulse shapes. For example, exponential or sinusoidal pulse shapes, or alternatively rectangular pulses and/or triangular pulses can be used. Furthermore it is advantageous for the voltage of the individual pulse to fluctuate within itself, for example sinusoidally. If DC voltage pulses are used, the polarity of the pulses can be reversed continuously or at intervals, thus allowing AC voltage pulses to be applied. Advantageously, a superposition of DC and AC voltages is also possible, to achieve optimal enrichment, separation and/or disintegration. It is equally possible, for example, to combine various pulse shapes and/or pulse intensities, i.e. voltage levels and pulse duration, in a variable manner; in the case of exponential pulse shapes the pulse duration is expressed by the time constant (xcfx84):xcfx84=CR(C: capacitance, R: resistance).
In a further advantageous embodiment of the invention it is also possible, for example, using suitable apparatus, to employ polyphase current, i.e. three-phase current. This allows the generation of, for example, sinusoidal AC voltages with a phase difference of 120xc2x0 or 240xc2x0.
In this context, the invention, in a preferred embodiment, provides for the use of pulse numbers, i.e. pulses per treatment duration, of at least 15, preferably from 15 to 19,000, especially from 5000 to 12,000. In a further preferred embodiment, the field strength of the pulses is far below the critical voltage Vc applied across the membrane or cell wall of the biological material, for example the cell or the liposome. Alternatively, however, according to the invention, a field strength of the pulses can be provided which is above the critical voltage Vc applied across the membrane or cell wall of the biological material. Preferably, the field strength of the pulses is from 0 to 200 V/cm, from 0.001 to 200 V/cm, from 0.01 to 200 V/cm, from 20 to 60 V/cm and particularly from 30 to 50 V/cm.
According to the invention it is possible, in a preferred embodiment, to let a pulse of high electric field strength be followed by a second pulse of lower field strength, in order thus to assist electrophoretic effects. Advantageously, the pulses can be superposed by means of DC voltage.
In a further preferred embodiment, the invention makes provision for carrying out the chromatographic separation and temperatures of between xe2x88x9230 and +90xc2x0 C., particularly from 50 to 55xc2x0 C. Particularly preferred are temperatures which, under the given constraints, are below the temperatures resulting in cell disruption and above or below the physiological, i.e. naturally obtaining temperatures of the biological material.
Advantageously, the invention, in a further preferred embodiment, makes provision for the disintegration to be carried out at temperatures of between 0 and 100xc2x0 C., particularly between 20 to 80xc2x0 C.
In a further preferred embodiment, the invention makes provision for the treatment duration, within which the separation is carried out via the use of pulsed, electric fields, to be from a few seconds, e.g. from 2 to 6 seconds, up to hours, e.g. from 3 to 5 hours.
In a further preferred embodiment, the invention makes provision for the frequency of the pulses to be from 0.1 Hz to 40 GHz.
Finally, the invention makes provision, in a further preferred embodiment, for the pulse duration to be from 25 ps to 50 min., particularly 15 xcexcs.
Electroporation and electrofusion, optionally in combination with dielectrophoresis, customarily involve the use of hypoosmolar media whose conductivity is as low as possible. Electrolytic effects, change in pH and release of cytotoxic ions from the electrodes are thus minimized. Since a main objective of these methods is to maintain the vitality of the cells, the composition of the medium is critical. A further reason for using such media in the methods listed is the shape of the cells in hypoosmolar solutions; they become rounder. This facilitates the calculation of the field strength to be used to achieve the critical voltage Vc, said field strength as a rule being lower for spherical objects. Moreover, the methods predominantly employ media having optimal potassium concentrations, to ensure the vitality of the treated cells. Apart from the osmolarity of the media and the presence of specific ions, conductivity is decisive. In the case of electroporation, electrofusion and dielectrophoresis, conductivity is low, as a rule. In general this is the only way to obtain the field strengths necessary to achieve the critical voltage Vc required for these methods.
Since the vitality of the cells in the case of the in situ separation methods according to the invention is not a major factor, these methods preferably employ isoosmolar media whose conductivities are high, compared with the conductivities customarily used with electroporation, electrofusion and dielectrophoresis. Even so, it is of course possible to employ hypo- or hyperosmolar media having comparatively low or high conductivities. Thus the in situ separation method can dispense with laborious xe2x80x9crebufferingxe2x80x9d of the samples. The biological material can be used directly as the xe2x80x9craw materialxe2x80x9d. The conductivity of the medium in the procedure according to the invention, i.e. the in situ separation method, can preferably be from 1 xcexcS/cm to 2 xcexcS/cm, particularly from 5 to 20 xcexcS/cm.
Pharmacologically relevant, low molecular weight proteins such as the human Macrophage Migration Inhibitory Factor (huMIF) cloned and expressed in E.coli, with a relative molecular mass of about 12.3 kDa can be purified from the respective cell suspensions via the in situ separation method according to the invention. The in situ separation method according to the invention can also be used in the field of bioreactors.
The method according to the invention can also be used for determining binding equilibria. The method according to the invention makes it possible for pores having a lifetime and size optimally tailored to the equilibrium in question to be induced in liposomes or other biological material. This offers the possibility of utilizing the principles of various methods of determining binding equilibria by means of a single method, i.e. the present method according to the invention. According to the invention it is also possible to employ liposomes filled with ligands, the ligands, after said liposomes have been permeabilized, being able to diffuse freely from the intracellular medium into the extracellular medium until an equilibrium has been established. According to the invention, provision can be made for macromolecules to which the ligands can bind to be present in the extracellular medium, so that the fraction of the bound ligands is removed from the equilibrium and ligands from the intracellular medium continue to flow in until the free fractions of the ligands in both chambers have equalized. After the equilibrium has been established, the concentration of the ligands in the extracellular medium then corresponds to the concentration of the free ligand in the association equilibrium of the intracellular medium. It is therefore possible, once the ligand concentration in the intracellular and extracellular medium has been determined, to determine the concentrations of the free and the bound ligand. Keeping the macromolecular concentration at various ligand concentration constant, it is then possible to determine binding constants.
According to the invention it is also possible for the macromolecule to be provided in the intracellular medium and for the ligand to be provided in the extracellular medium. As an alternative to liposomes, biological cells can of course be used.
According to the invention it is therefore possible for the binding characteristics of macromolecules intrinsic to cells or of expressed macromolecules extrinsic to cells in terms of a specific ligand to be studied in situ.
The invention also relates to the use of pulsed electric fields for the selective in situ separation of substances, the substances being concentrated either in a liquid medium which surrounds biological material or within the biological material, pulse numbers of at least 15, preferably from 15 to 19000, particularly from 5000 to 12000, being used in generating the pulsed electric fields.
In a preferred embodiment, provision is made for the samples to be treated to be applied to matrices, for example membranes or bonded fiber webs. The matrices can either be in direct contact with the conductive elements or, for example, be separated from the conductive elements by liquid zones.
In a further preferred embodiment of the invention, provision is made for the samples to be treated, especially doped matrices or liquids which comprise the biological material, not to be in direct contact with the conductive elements, for example the sample mount system. The contact can advantageously be broken by air, for example by conductive elements not being immersed in the liquid and/or by conductive elements being encased by nonconductive elements. In order to achieve, in particular, field strengths of up to 200 V/cm in the samples thus prepared it is advantageous for higher voltages if required, possibly as a function of the spacing of the conductive elements, to be used on the conductive elements. As the electrical separation, disintegration or enrichment methods permit the preferable use of pulsed electric fields having very low field strengths or advantageously do not require any direct contact of the conductive elements with the sample, the choice of solvent is not restricted. It is possible, for. example, for biological material to be disrupted or enriched or separated even in solutions having high specific conductivities, without incurring the risk of spark discharges. In particular, this provides the option of combining the electrical separation, enrichment and/or disintegration with chemical methods.
In an advantageous refinement of the invention provision is made for the optional use of certain salts, for example chaotropic salts, and detergents, enzymes and others before or during the electrical separation and/or disintegration of course it is also possible to carry out a chemical after-treatment of the separated or disintegrated samples or suspensions obtained. Advantageously, the combination of a chemical separation, enrichment and/or disintegration with the enrichment, separation and/or disintegration induced or accompanied by electric fields can lead not only to a simple addition of the effects, but also to unexpected and novel synergetic effects.
Chemicals which change and/or stabilize the specific conductivity of the extracellular phase of the cell membrane and possibly the cell interior, can be used to advantage. This has an advantageous effect on the differential potential across the cell membrane, resulting in a change, for example, in the critical voltage across the cell membrane, which is necessary to generate pores, discrete lesions and/or ruptures in the cell membrane. Also possible is the use of suitable chemicals which affect and/or modify the fluidity of the cell membranes. Similarly to the way in which an increase in temperature affects the fluidity of the cell membrane, with an effect on the value of the critical cell membrane voltage, chemicals can advantageously likewise affect the fluidity of the cell membrane, particularly the critical cell membrane voltage. Chemicals and changes in temperature can therefore affect the fluidity of the cell membrane, resulting in an effect on the value of the critical cell voltage. The chemicals may optionally also have additive, lytic properties. Furthermore, the addition of chemicals can advantageously lead to reduced breakdown of cell constituents. For example, the chemical inhibition of nucleases and/or proteases in the extraction of nucleic acids and/or proteins via electrical cell disruption can be of advantage. But other cell constituents, for example metabolites, can likewise be stabilized in this way while being released and after they have been released by electrical cell disruption, particularly during the separation and/or disintegration.
The invention also relates to an apparatus which comprises an nonconductive element and at least two conductive elements, particularly electrodes. In a preferred embodiment, provision is made for the nonconductive element to be designed as a holding means and for conductive elements to be capable of being connected, for example via a cover, to the holding means in such a way that the sample can be disintegrated in the holding means. Alternatively, however, provision can advantageously be made for the holding means to comprise a conductive element. The conductive elements, can include a nonconductive element to allow a voltage to be built up, but it is also possible for the holding means to comprise just a first conductive element and for the second conductive element to be disposed in such a way in a cover for the holding means that it can be positioned so as to be capable of effective connection to the first conductive element designed as a holding means.
The invention also relates to an apparatus for implementing the method according to the invention, particularly a sample mount system or an in situ separation apparatus, the latter being designed as a preferably essentially box-shaped, particularly cuboid housing comprising a baseplate, a cover plate, two side walls and two electrodes designed as side walls. The cover plate has at least one port, with the option of further ports being provided in the cover plate and possibly in the baseplate. These ports can in each case be sealed by a filter which is used to separate off the separated substance or substance mixture. The electrodes can be made of aluminum, alloy steel, carbon, platinum, gold or silver or comprise these on their own or in combination. Preferably, the sample mount system according to the invention also comprises a voltage generator, particularly an HVA apparatus (high voltage apparatus), a frequency generator and a pulse generator.
To enable a high sample throughput in the electrical selective separation, sorting and/or disintegration, it is advantageous to provide separation apparatuses which allow a plurality of samples to be treated in one go. This can be advantageously implemented, for example, by various formats, such as those used in known microtiter plate systems. One example of an advantageous way of generating electric fields involves novel array systems which, for example, consist of a sample mount and a cover. In this way, conductive and nonconductive elements can be advantageously tailored to one another by different arrangements of conductive and nonconductive elements of the sample mounts and the covers, relative to one another. Regarding the covers, for example, cylindrical metal rods, with an additional conductive plate in the cover of the sample mount or at the end of the metal rod can be used. That end of the metal rods which projects into the sample can advantageously be in the form of a sphere. Partial or complete insulation of the metal rods or conductive elements of the cover plate of the separation apparatus and/or of the entire separation apparatus and/or of the sample mount can be of advantage and advisable. Separation apparatuses for the selective separation, and sample mounts for the disintegration, can advantageously be used for the processes of disintegration, separation and/or isolation. To design electrical disintegration arrays so as to be compatible with other methods, there is an advantage in using standardized dimensions. For example, it is advantageous to tailor such an electrical disintegration array or, for example, an individual sample mount to the dimensions of sample mount-containing known PCR instruments, fluorimeters, spectrophotometers and the like. In this context it is particularly advantageous to provide transparent regions, for example in the nonconductive elements, especially the baseplates.
Further advantageous embodiments of the invention can be gathered from the dependent claims.